A5082311613- Olfactory and Sensory Function Studies
- Advanced Chemical Sensor Technologies
- DNA and Nucleic Acid Chemistry
- DNA Repair Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Genomics and Chromatin Dynamics
- Genomic variations and chromosomal abnormalities
- RNA and protein synthesis mechanisms
- Long-Term Effects of COVID-19
- Mitochondrial Function and Pathology
- Carcinogens and Genotoxicity Assessment
- Autism Spectrum Disorder Research
- Cancer Genomics and Diagnostics
- COVID-19 Clinical Research Studies
- Congenital heart defects research
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- ATP Synthase and ATPases Research
- Bioinformatics and Genomic Networks
- Biochemical Analysis and Sensing Techniques
- Protein Structure and Dynamics
- Metabolomics and Mass Spectrometry Studies
- Gene expression and cancer classification
- Evolution and Genetic Dynamics
Columbia University
2021-2024
University of Lausanne
2014-2021
Brain (Germany)
2021
Taras Shevchenko National University of Kyiv
2008-2013
Noncoding variation and gene expression Natural genetic outside of protein coding regions affects multiple molecular phenotypes that can differ across individuals. To examine how genomic proximal (cis) or distal (trans) regulation, Delaneau et al. analyzed expression, chromatin, the three-dimensional conformation genome. Clustering regulatory elements activity individuals reveals structures termed cis-regulatory domains trans-regulatory hubs affect expression. Associations between these...
The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying COVID biology, we compared short- and long-term systemic responses golden hamster after either SARS-CoV-2 influenza A virus (IAV) infection. Results demonstrated that exceeded IAV its capacity cause permanent injury lung kidney uniquely...
Anatomical structures and mechanisms linking genes to neuropsychiatric disorders are not deciphered. Reciprocal copy number variants at the 16p11.2 BP4-BP5 locus offer a unique opportunity study intermediate phenotypes in carriers high risk for autism spectrum disorder (ASD) or schizophrenia (SZ). We investigated variation brain anatomy deletion duplication carriers. Beyond gene dosage effects on global metrics, we show that of genomic copies negatively correlated gray matter volume white...
Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements associated with autism spectrum disorders mirror phenotypes obesity/underweight macrocephaly/microcephaly. Such were previously non-overlapping proximal 600 BP4-BP5 interval. These two CNV-prone regions at reciprocally engaged in complex chromatin looping, as...
Abstract We investigated the mechanisms of DNA exit during single‐cell gel electrophoresis (the comet assay) by measuring kinetics tail formation. In neutral assay, rate was found to be dependent on topological state DNA, which influenced either ethidium bromide or a low radiation dose. The results clearly show that is formed extended loops: loop extension, being reversible when torsional constraint remains in loops, favored relaxed. formation case high dose points out accumulation...
Abstract Olfaction relies on a coordinated partnership between odorant flow and neuronal communication. Disruption in our ability to detect odors, or anosmia, has emerged as hallmark symptom of infection with SARS-CoV-2, yet the mechanism behind this abrupt sensory deficit remains elusive. Here, using molecular evaluation human olfactory epithelium (OE) from subjects succumbing COVID-19 hamster model SARS-CoV-2 infection, we discovered widespread downregulation receptors (ORs) well key...
SUMMARY SARS-CoV-2 has been found capable of inducing prolonged pathologies collectively referred to as Long-COVID. To better understand this biology, we compared the short- and long-term systemic responses in golden hamster following either or influenza A virus (IAV) infection. While exceeded IAV its capacity cause injury lung kidney, most significant changes were observed olfactory bulb (OB) epithelium (OE) where inflammation was visible beyond one month post Despite a lack detectable...
Despite the recent advances in understanding mechanisms of olfaction, no tools are currently available to noninvasively identify loss smell. Because substantial increase patients presenting with coronavirus disease 2019–related smell, pandemic has highlighted urgent need develop quantitative methods. <b>Methods:</b> Our group investigated use a novel fluorescent probe named Tsp1a-IR800<sub>P</sub> as tool diagnose targets sodium channel 1.7, which plays critical role olfaction by aiding...
Ultra long-range genomic contacts, which emerge as prominent components of genome architecture, constitute a biochemical paradox. This is because regulatory DNA elements make selective and stable contacts with sequences located megabases away, instead interacting proximal occupied by the same exact transcription factors (TF). exemplified in olfactory sensory neurons (OSNs), where only fraction Lhx2/Ebf1/Ldb1-bound sites interact each other, converging into highly multi-chromosomal enhancer...
Summary Genome-wide studies on the genetic basis of gene expression and structural properties chromatin have considerably advanced our understanding function human genome. However, it remains unclear how structure relates to and, in this work, we aim at bridging both by assembling a dataset that combines activity regulatory elements (e.g. enhancers promoters), genes variations 317 individuals across two cell types. We show is structured within 12,583 Cis Regulatory Domains (CRDs) are type...
In single-cell gel electrophoresis (the comet assay) the DNA of lysed cells, nucleoids, extends towards anode in a track resembling tail.The aim this work was to investigate effects changes topology on process.Methods.We used kinetic approach, proposed earlier by us, measure relative amount tails as function time presence different concentrations chloroquine, widely intercalator.Results.We have shown that, at given small concentrations, intercalation chloroquine strongly facilitates tail...
Abstract Mutational spectrum of the mitochondrial genome (mtDNA) does not resemble signatures any known mutagens and variation in mtDNA mutational spectra between different tissues organisms is still incomprehensible. Since mitochondria tightly involved aerobic energy production, it expected that may be affected by oxidative damage which increasing with cellular organismal aging. However, well-documented signature damage, G>T substitutions, typical only for nuclear while extremely rare...
The kinetics of DNA exit during single cell gel electrophoresis (comet assay) human lymphocytes has been investigated.The was carried out at neutral pH either in the absence or presence different ethidium bromide concentrations.The demonstrated dependence efficiency on concentration indicates that comet tail consists loop domains extended by electric field.The is essentially favored when torsional constraint relaxed.In contrast, disappearance after switching off field observed if some level...
The sense of smell (olfaction) is one the most important senses for animals including humans. Despite significant advances in understanding mechanism olfaction, currently, there are no objective non-invasive methods that can identify loss smell. Covid-19-related has highlighted need to develop olfaction. Voltage-gated sodium channel 1.7 (Na
Abstract The mutational spectrum of the mitochondrial DNA (mtDNA) does not resemble any known signatures nuclear genome and variation in mtDNA spectra between different organisms is still incomprehensible. Since mitochondria tightly involved aerobic energy production, it expected that affected by oxidative damage. Assuming damage increases with age, we analyze mutagenesis species. Analysing (i) dozens thousands somatic mutations samples age (ii) 70053 polymorphic synonymous substitutions,...
The SARS-CoV-2 virus rarely infects olfactory sensory neurons, yet causes widespread anosmia. Explaining this seeming paradox is that odor detection impaired due to virus-mediated disruption of nuclear architecture results in receptor and associated downregulation signaling genes.
SARS-CoV-2 infects less than 1% of cells in the human body, yet it can cause severe damage a variety organs. Thus, deciphering non-cell autonomous effects infection is imperative for understanding cellular and molecular disruption elicits. Neurological cognitive defects are among least understood symptoms COVID-19 patients, with olfactory dysfunction being their most common sensory deficit. Here, we show that both humans hamsters causes widespread downregulation receptors (OR) signaling...